Endothelial PDGF-CC regulates angiogenesis-dependent thermogenesis in beige fat.
journal contributionposted on 11.11.2016, 10:17 by T. Seki, K. Hosaka, S. Lim, C. Fischer, J. Honek, Y. Yang, P. Andersson, M. Nakamura, E. Näslund, S. Ylä-Herttuala, M. Sun, H. Iwamoto, X. Li, Y. Liu, Nilesh J. Samani, Yihai Cao
Cold- and β3-adrenoceptor agonist-induced sympathetic activation leads to angiogenesis and UCP1-dependent thermogenesis in mouse brown and white adipose tissues. Here we show that endothelial production of PDGF-CC during white adipose tissue (WAT) angiogenesis regulates WAT browning. We find that genetic deletion of endothelial VEGFR2, knockout of the Pdgf-c gene or pharmacological blockade of PDGFR-α impair the WAT-beige transition. We further show that PDGF-CC stimulation upregulates UCP1 expression and acquisition of a beige phenotype in differentiated mouse WAT-PDGFR-α(+) progenitor cells, as well as in human WAT-PDGFR-α(+) adipocytes, supporting the physiological relevance of our findings. Our data reveal a paracrine mechanism by which angiogenic endothelial cells modulate adipocyte metabolism, which may provide new targets for the treatment of obesity and related metabolic diseases.